Author Correction: Discovery of new genetic loci for male sexual orientation in Han population.
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ABSTRACT:
SUBMITTER: Hu SH
PROVIDER: S-EPMC8633345 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
Publications
Author Correction: Discovery of new genetic loci for male sexual orientation in Han population.
Hu Shao-Hua SH Li Hai-Mei HM Yu Hao H Liu Yan Y Liu Chen-Xing CX Zuo Xian-Bo XB Lu Jing J Jiang Jia-Jun JJ Xi Cai-Xi CX Huang Bo-Chao BC Xu Hu-Ji HJ Hu Jian-Bo JB Lai Jian-Bo JB Huang Man-Li ML Liu Jian-Ning JN Xu Dan-Ge DG Guo Xi-Chao XC Wu Wei W Wu Xin X Jiang Lei L Li Meng M Zhang Guang-Ping GP Huang Jin-Wen JW Wei Ning N Lv Wen W Duan Jin-Feng JF Qi Hong-Li HL Hu Chan-Chan CC Chen Jing-Kai JK Zhou Wei-Hua WH Xu Wei-Juan WJ Liu Chen-Feng CF Liang Hai-Yong HY Du Jing J Zheng Shu-Fa SF Lu Qiao-Ling QL Zheng Lin L Hu Xiao-Wei XW Chen Feng-Xiang FX Chen Peng P Zhu Biao B Xu Li-Jun LJ Ni Zhi-Min ZM Fang Ye-Zhen YZ Yang Zuo-Kai ZK Shan Xin-Ren XR Zheng En-de ED Zhang Fan F Zhou Qing-Qing QQ Rao Yi Y Swaab Dick D Yue Wei-Hua WH Xu Yi Y
Cell discovery 20211130 1
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Project description:Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, Pmeta = 8.36 × 10-8, OR = 1.29; rs7259428, 19q12, ZNF536, Pmeta = 7.58 × 10-8, OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese (n = 4791) and European ancestries (n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1, Pmeta = 1.95 × 10-8; rs2414487, 15q21.3, LOC145783, Pmeta = 4.53 × 10-9; rs2106525, 7q31.1, MDFIC, Pmeta = 6.24 × 10-9). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice.
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Project description:Family and twin studies suggest that genes play a role in male sexual orientation. We conducted a genome-wide association study (GWAS) of male sexual orientation on a primarily European ancestry sample of 1,077 homosexual men and 1,231 heterosexual men using Affymetrix single nucleotide polymorphism (SNP) arrays. We identified several SNPs with p < 10-5, including regions of multiple supporting SNPs on chromosomes 13 (minimum p = 7.5 × 10-7) and 14 (p = 4.7 × 10-7). The genes nearest to these peaks have functions plausibly relevant to the development of sexual orientation. On chromosome 13, SLITRK6 is a neurodevelopmental gene mostly expressed in the diencephalon, which contains a region previously reported as differing in size in men by sexual orientation. On chromosome 14, TSHR genetic variants in intron 1 could conceivably help explain past findings relating familial atypical thyroid function and male homosexuality. Furthermore, skewed X chromosome inactivation has been found in the thyroid condition, Graves' disease, as well as in mothers of homosexual men. On pericentromeric chromosome 8 within our previously reported linkage peak, we found support (p = 4.1 × 10-3) for a SNP association previously reported (rs77013977, p = 7.1 × 10-8), with the combined analysis yielding p = 6.7 × 10-9, i.e., a genome-wide significant association.
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Project description:BackgroundShaanxi province, located in the upper Yellow River, has been evidenced as the geographic origin of Chinese civilization, Sino-Tibetan-speaking language, and foxtail or broomcorn millet farmers via the linguistic phylogenetic spectrum, archeological documents, and genetic evidence. Nowadays, Han Chinese is the dominant population in this area. The formation process of modern Shaanxi Han population reconstructed via the ancient DNA is on the way, however, the patterns of genetic relationships of modern Shaanxi Han, allele frequency distributions of high mutated short tandem repeats (STRs) and corresponding forensic parameters are remained to be explored.MethodsHere, we successfully genotyped 23 autosomal STRs in 630 unrelated Shaanxi male Han individuals using the recently updated Huaxia Platinum PCR amplification system. Forensic allele frequency and parameters of all autosomal STRs were assessed. And comprehensive population genetic structure was explored via various typical statistical technologies.ResultsPopulation genetic analysis based on the raw-genotype dataset among 15,803 Eurasian individuals and frequency datasets among 56 populations generally illustrated that linguistic stratification is significantly associated with the genetic substructure of the East Asian population. Principal component analysis, multidimensional scaling plots and phylogenetic tree further demonstrated that Shaanxi Han has a close genetic relationship with geographically close Shanxi Han, and showed that Han Chinese is a homogeneous population during the historic and recent admixture from the STR variations. Except for Sinitic-speaking populations, Shaanxi Han harbored more alleles sharing with Tibeto-Burman-speaking populations than with other reference populations. Focused on the allele frequency correlation and forensic parameters, all loci are in accordance with the minimum requirements of HWE and LD. The observed combined probability of discrimination of 8.2201E-28 and the cumulative power of exclusion of 0.9999999995 in Shaanxi Han demonstrated that the studied STR loci are informative and polymorphic, and this system can be used as a powerful routine forensic tool in personal identification and parentage testing.ConclusionBoth the geographical and linguistic divisions have shaped the genetic structure of modern East Asian. And more forensic reference data should be obtained for ethnically, culturally, geographically and linguistically different populations for better routine forensic practice and population genetic studies.
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Project description:Male sexual functioning is a prerequisite for conception and consequently for reproduction and is thus a crucial mechanism from an evolutionary and social perspective. Previous studies reported better sexual functioning in coupled compared to single individuals. However, it is not clear whether sexual functioning increases or decreases with a short-term casual sexual strategy, which is another possibility, along with a long-term strategy. Furthermore, sexual orientation may represent yet another mating strategy that may influence sexual functioning. Here, we aimed to test the possible associations between male sexual functioning and sexual strategies, as measured through sociosexuality, relationship status, and sexual orientation. We hypothesize that due to its relationship with the evolved motivation of mate acquisition and mate retention, both stable relationships and sociosexuality would be positively associated with male sexual functioning. We did not expect significant differences in sexual functioning among men with different sexual orientations. We sampled 427 healthy men of different sexual orientations (203 heterosexuals, 77 bisexuals, and 147 gay men) who completed the Male Sexual Function Index (MSFI) and its subscales of desire, arousal, erection, orgasm, and satisfaction; the Sociosexual Orientation Inventory-Revised; and sociodemographic questions. A multivariate general linear model showed that, compared to single individuals, partnered individuals reported greater MSFI-arousal, MSFI-erection, MSFI-orgasm, and MSFI-satisfaction. Sociosexuality and sexual orientation only weakly predicted MSFI domains. Male sexual functioning thus seems to be moderately associated with a long-term mating strategy and can thus serve for relationship maintenance rather than for acquiring new partners.
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Project description:Several biological mechanisms have been proposed to influence male sexual orientation, but the extent to which these mechanisms cooccur is unclear. Putative markers of biological processes are often used to evaluate the biological basis of male sexual orientation, including fraternal birth order, handedness, and familiality of same-sex sexual orientation; these biomarkers are proxies for immunological, endocrine, and genetic mechanisms. Here, we used latent profile analysis (LPA) to assess whether these biomarkers cluster within the same individuals or are present in different subgroups of nonheterosexual men. LPA defined four profiles of men based on these biomarkers: 1) A subgroup who did not have these biomarkers, 2) fraternal birth order, 3) handedness, and 4) familiality. While the majority of both heterosexual and nonheterosexual men were grouped in the profile that did not have any biomarker, the three profiles associated with a biomarker were composed primarily of nonheterosexual men. We then evaluated whether these subgroups differed on measures of gender nonconformity and personality that reliably show male sexual orientation differences. The subgroup without biomarkers was the most gender-conforming whereas the fraternal birth order subgroup was the most female-typical and agreeable, compared with the other profiles. Together, these findings suggest there are multiple distinct biodevelopmental pathways influencing same-sex sexual orientation in men.
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Project description:BackgroundGenetic polymorphisms at 23 short tandem repeat (STR) loci were investigated in 1,215 Jining Han individuals from Jining city, Shandong province, eastern China.MethodsWe used population genetic data of 23 autosomal STR loci included in the Huaxia Platinum system to evaluate 1,215 unrelated Chinese Han individuals in the Jining Han population. Allele frequencies and forensic parameters of the STR loci were determined and genetic relationships among the Jining Han and other Chinese populations were evaluated.ResultsIn total, we observed 321 alleles, with frequencies ranging from 0.00041 to 0.52222. The combined discrimination power and probability of excluding paternity were 0.99999999999999999999999999919 and 0.99999999962, respectively. No deviations from HWE were observed at any loci. Population comparisons showed that the Xinjiang groups (Uyghur and Kazakh) and the Mongolian and Tibetan groups were isolated, while the Jining Han population clustered together with other populations, except the Guizhou Han population.ConclusionThis study demonstrated that 23 autosomal STR loci included in the Huaxia Platinum system are highly polymorphic and suitable for personal forensic identification and paternity testing in this population.
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Project description:Previous neuroimaging studies demonstrated sex and also sexual orientation related structural and functional differences in the human brain. Genetic information and effects of sex hormones are assumed to contribute to the male/female differentiation of the brain, and similar effects could play a role in processes influencing human's sexual orientation. However, questions about the origin and development of a person's sexual orientation remain unanswered, and research on sexual orientation related neurobiological characteristics is still very limited. To contribute to a better understanding of the neurobiology of sexual orientation, we used magnetic resonance imaging (MRI) in order to compare regional cortical thickness (Cth) and subcortical volumes of homosexual men (hoM), heterosexual men (heM) and heterosexual women (heW). hoM (and heW) had thinner cortices primarily in visual areas and smaller thalamus volumes than heM, in which hoM and heW did not differ. Our results support previous studies, which suggest cerebral differences between hoM and heM in regions, where sex differences have been reported, which are frequently proposed to underlie biological mechanisms. Thus, our results contribute to a better understanding of the neurobiology of sexual orientation.
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Project description:Male sexual orientation is a scientifically and socially important trait shown by family and twin studies to be influenced by environmental and complex genetic factors. Individual genome-wide linkage studies (GWLS) have been conducted, but not jointly analyzed. Two main datasets account for > 90% of the published GWLS concordant sibling pairs on the trait and are jointly analyzed here: MGSOSO (Molecular Genetic Study of Sexual Orientation; 409 concordant sibling pairs in 384 families, Sanders et al. (2015)) and Hamer (155 concordant sibling pairs in 145 families, Mustanski et al. (2005)). We conducted multipoint linkage analyses with Merlin on the datasets separately since they were genotyped differently, integrated genetic marker positions, and combined the resultant LOD (logarithm of the odds) scores at each 1 cM grid position. We continue to find the strongest linkage support at pericentromeric chromosome 8 and chromosome Xq28. We also incorporated the remaining published GWLS dataset (on 55 families) by using meta-analytic approaches on published summary statistics. The meta-analysis has maximized the positional information from GWLS of currently available family resources and can help prioritize findings from genome-wide association studies (GWAS) and other approaches. Although increasing evidence highlights genetic contributions to male sexual orientation, our current understanding of contributory loci is still limited, consistent with the complexity of the trait. Further increasing genetic knowledge about male sexual orientation, especially via large GWAS, should help advance our understanding of the biology of this important trait.
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